Antibody-Mediated Rejection Due to Donor-Specific HLA-DQB1 and DQA1 Antibodies After Kidney Transplantation: A Case Report

Abstract

BackgroundDonor-specific HLA antibody (DSA) is associated with the risk of allograft loss due to antibody-mediated rejection (ABMR). The majority of de novo DSA after kidney transplantation is directed toward donor HLA-DQ antigens. A HLA-DQ antigen is a heterodimer consisting of an alpha and beta chain. Traditionally, HLA-DQA1 typing has not been part of the pretransplant evaluation. Therefore, DQ alpha proteins are not usually taken into account in the interpretation of HLA-DQ antibody reactions. MethodsWe hereby present a case of a kidney transplant recipient with 0% pretransplant panel reactive antibody. She received kidney allograft from her husband. Two years after transplantation, she experienced abdominal swelling, and enlargement of transplanted kidney was identified. A biopsy of the allograft kidney demonstrated chronic active ABMR. DSAs were investigated using immunoglobulin G (IgG) and C1q single antigen bead (SAB) assay. HLAMatchmaker analysis was performed to identify eplets that explain the antibody reactivity patterns. ResultsThe IgG SAB analysis of a patient’s serum at the time of rejection showed positive reactions with all DQ2-carrying beads with mean fluorescence intensity (MFI) > 10000. However, the C1q assay demonstrated strong reaction to only HLA-DQA1∗05:01-DQB1∗02:01-carrying bead with MFI = 22462, whereas weak or no reactions against other HLA-DQ2-carrying beads were found. High-resolution HLA typing revealed that HLA-DQA1∗05:01 and DQB1∗02:01 were mismatched donor antigens. HLAMatchmaker analysis showed that the antibodies were reactive toward 40GR3 eplet on DQA1 and 45GE3 eplet on DQB1. ConclusionsThis case highlights the clinical significance of antibodies specific to both DQ alpha and DQ beta chains after kidney transplantation.